This study investigated the utility of measuring plasma long pentraxin 3 (PTX3) levels in the early detection of endothelial dysfunction compared with Von Willebrand factor (vWF) activity and flow-dependent arterial dilatation (well-known markers of endothelial dysfunction) in early diabetic nephropathy.

Materials and methods

A total of 50 Egyptian patients with type 2 diabetes and 20 healthy controls were recruited from the Diabetes, Endocrinology and Metabolism center, Faculty of Medicine, Cairo University. The diabetic patients were divided into two equal groups of comparable age and sex: group I consisted of patients with normal urinary albumin excretion and group II consisted of patients with microalbuminuria.

Results

In group II, the plasma PTX3 level was significantly higher (median value 2.3 ng/ml) and the mean flow-mediated dilatation (FMD; 0.433±0.059) was significantly lower when compared with the control group (PTX3 1.15 ng/ml, FMD 0.901±0.04; P<00001) and with group I (PTX3 1.2 ng/ml, FMD 0.627±0.05; P<0.0001). The vWF activity (median value) was significantly higher in the two diabetic groups compared with controls (20.2, 16.3 and 4% in group I, group II, and controls, respectively; P<0.0001), with no significant difference between the two diabetic groups. There was a significant positive correlation between PTX3 levels and vWF activity (P<0.001), diabetes duration, and concentration of fasting blood sugar, HbA1c, cholesterol, and triglyceride and a significant negative correlation between PTX3 levels and FMD (P<0.001) in all diabetic patients. In group II, there was a significant positive correlation between PTX3 levels and vWF activity (r=0.603, P=0.001).

Conclusion

PTX3 may represent a useful endothelial dysfunction marker in early diabetes nephropathy.

Although there are considerable data on the changes in left ventricular function in hemodialysis (HD) patients, only a few studies on right ventricular (RV) function can be found in the literature. We investigated the changes in RV function in HD patients.

Methods

We examined 74 individuals grouped as follows: healthy controls (n=24) and HD patients (n=50). Echocardiography including tissue Doppler imaging (TDI) of the RV was performed in all patients.

Subclinical RV dysfunction – as estimated by RV function indices; tricuspid plane systolic excursion, right ventricle fractional area change, and LTDISº – is increased among HD patients. A high prevalence of pulmonary hypertension was found among HD patients and this was not associated significantly with RV or left ventricular dysfunction in these patients.

Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. Diabetic nephropathy is the major microvascular complication of diabetes mellitus; one of the earliest clinical signs of diabetic nephropathy is an elevated urinary albumin excretion (UAE), referred to as microalbuminuria. Fractalkine is a large cytokine protein of 373 amino acids; it contains multiple domains. Fractalkine (CX3CL1) is a unique chemokine and the only representative of the CX3C group. It exists as a membrane-bound and soluble form. It interacts with cells expressing CX3CR1, a G-coupled protein receptor. It is also commonly known by the names fractalkine (in humans) and neurotactin (in mice).

Aim

Our study aimed to assess fractalkine levels in type 2 Egyptian diabetic patients with and without diabetic nephropathy and its role as a marker in the development of diabetic nephropathy.

Our study showed that the serum fractalkine concentration was significantly elevated in type 2 diabetic patients with nephropathy (1153.14±261.1) compared with type 2 diabetic patients without nephropathy (705.78±150.59) and the control group (251.5±64) (both P=0.000). There was a significant correlation between serum fractalkine level and 24-h UAE, HBA1C, and serum creatinine. Thus, this positive correlation between serum fractalkine level and UAE could be an early predictor of microvascular complications in diabetic patients. We can conclude that serum fractalkine plays a pathogenic role in the development of diabetic nephropathy.

Dyslipidemia has long been implicated in diabetic complications. However, many subgroups have been considered to be responsible. Furthermore, a cause and effect relationship has long been debated. Apolipoprotein B (Apo B) is an exact measure of the total number of very low-density lipoprotein and low-density lipoprotein particles; thus, total plasma Apo B is a reliable surrogate for actual low-density lipoprotein particle number irrespective of its size. Hence, it is a better indicator of the correlation between dyslipidemia and diabetic microvascular complications.

Aim of the work

Our aim is to study the correlation between Apo B and diabetic microvascular complications, namely, nephropathy and retinopathy.

Materials and methods

A cross sectional study was carried out of 56 diabetic patients, 36 men and 20 women, both type 1 and 2, who were chosen randomly from the outpatient Endocrinology Clinic in Cairo University. Serum creatinine, estimated glomerular filtration rate, urine albumin/creatinine ratio (A/C ratio), and Apo B levels were determined. Groups were divided according to the A/C ratio as follows: no proteinuria (A/C ratio<30 mg/g), incipient proteinuria (30–300 mg/g), and overt proteinuria (>300 mg/g). We performed fundus examination as well as fluorescein angiography in patients with retinopathy. Patients on dialysis, HBA1c more than 7.5, on lipid-lowering treatment, or with familial hyperlipidemia were excluded. Calculations were carried out using the SPSS v.10 statistical software.

Results

We found a significant positive correlation between Apo B levels and microvascular complications. Apo B was higher with overt nephropathy than incipient nephropathy (1.75±0.38), and higher in patients with incipient nephropathy (1.4±0.48) than in patients without nephropathy (1.02±0.34, P<0.01).

A highly significant correlation was detected between the grades of retinopathy and the Apo B level. Finally, a significant positive correlation was detected between the presence of maculopathy and Apo B. Apo B levels were significantly higher in the presence of both nephropathy and retinopathy (1.26±0.389) than in the absence of both complications (0.77±0.361, P<0.05).

Conclusion

Apo B levels are strongly correlated to diabetic microvascular complications. The higher the degree of nephropathy, the higher the Apo B level. The presence of more than one microvascular complication correlates positively with high levels of Apo B. This suggests the possible use of Apo B as a sensitive biomarker of the presence of early diabetic microvascular complications.

As cardiovascular disease is the leading cause of mortality in type 2 diabetes mellitus, new markers for early detection and risk stratification of diabetic macroangiopathy and microangiopathy are highly desired. Adipocytokines were considered to lead to an increased risk of vascular complications in patients with type 2 diabetes by modulating vascular function and affecting the inflammatory process, thus enhancing atherosclerosis. Two of these were of particular interest, namely, visfatin and adiponectin.

Aim

The aim of this study was to evaluate serum visfatin, serum, and urinary adiponectin as early, sensitive surrogate markers of vascular atherosclerosis. We also correlated the levels of these markers to the degree of carotid intimal medial thickness (reflecting the atherosclerotic burden) in type 2 diabetic patients.

Results

Sixty diabetic patients were subdivided into two groups: group I (30 patients with carotid atherosclerosis as assessed by carotid Doppler) and group II (30 patients without carotid atherosclerosis). Twenty healthy volunteers participated as controls. Serum visfatin as well as serum and urinary adiponectin were assessed in all the study groups. We found significantly higher levels of serum visfatin among diabetics compared with the control group. Visfatin was also significantly higher in group I diabetics with atherosclerosis than those without (P<0.05). Similarly, urinary adiponectin was significantly higher in group I than in group II and in diabetics than in the control group. Serum adiponectin was higher in the control group than both the study groups. Using a regression model, visfatin proved to be the only significant predictor in the model (β=0.03, P<0.001). In fact, visfatin alone proved significant, explaining 63% of the variability in carotid intima-media thickness (P<0.001).

Conclusion

Serum visfatin is highly correlated with macrovascular complications in diabetic patients. Serum visfatin may emerge as a valuable and cheaper surrogate marker for the prediction of prevalent macrovascular complications in a type 2 diabetic population. It is a novel and easy-to-obtain method for the clinical assessment of vascular stress and cardiovascular disease risk in type 2 diabetes. Future prospective studies are needed to confirm our results.

Renalase gene polymorphisms in patients with type 2 diabetes mellitus with and without hypertension

p. 149

Wael Refaie, Ahmad ElewaDOI:10.7123/01.EJIM.0000432881.43500.97

Background

Blood pressure (BP) is acutely regulated by the sympathetic nervous system through the action of vasoactive hormones (epinephrine, norepinephrine, and dopamine). Renalase, a recently discovered enzyme with monoamine oxidase activity is implicated in the degradation of catecholamines with a possible role in BP maintenance and cardiac protection against hypertension (HTN) and cardiovascular (CV) events.

Objectives

The aim of this study was to identify the potential involvement of renalase gene polymorphisms in patients with type 2 diabetes mellitus (T2DM) with or without HTN in the absence of diabetic nephropathy and to illustrate the role of renalase gene single-nucleotide polymorphisms (rs2576178 and rs10887800) in CV events.

Study design

This was a cross-sectional study.

Patients and methods

A total of 180 patients with T2DM attending the diabetes and cardiology clinics of Mansoura Hospital were recruited in the study: 100 patients with T2DM with HTN and 80 patients with T2DM who were normotensive. Further, 50 apparently healthy individuals matched in age and sex were included as a reference group. Clinical and laboratory examinations stressing on symptoms and signs of diabetes and HTN complications and ECG and Holter ECG monitoring stressing on QTc and QTd were performed; BMI, lipograms, microalbumin levels, and serum creatinine levels were also determined. Patients with renal disease, hepatic disease, and heart failure, those with previous or present renal or suprarenal lesions or endocrinopathies, and those with secondary HTN were excluded from the study. Genotype determination for two single-nucleotide polymorphisms (rs2576178 and rs10887800) in the renalase gene was carried out using the PCR method.

Results

The frequency of the GG allele of rs2576178 and rs10887800 was insignificantly higher in the diabetic hypertensive group than in the diabetic normotensive group. Both diabetic groups showed higher levels of GG alleles than the control group. The frequency of the GA allele of rs2576178 was significantly higher in the diabetic hypertensive group in comparison with the normotensive diabetic group. The allele frequency of G and A alleles of both studied renalases was also higher in the diabetic hypertensive group in comparison with the diabetic normotensive group; however, the differences were insignificant. The genotype distribution and allele frequencies did not show any statistically significant association with BMI, neuropathy, retinopathy, myocardial ischemia, QTc, or QTd.

Conclusion

The renalase gene can be potentially involved in BP regulation in T2DM. Further large-scale studies on the relationship between renalase and acute coronary syndrome and CV events are warranted.

Diabetic foot problems are highly prevalent, responsible for almost 50% of all diabetes-related hospital admissions and a 10-year reduction in life expectancy. The main factors involved in the pathology of diabetic foot are neuropathy, ischemia, and infection. The comorbidities of diabetes are hypertension, obesity, and dyslipidemia. Because of the huge premature morbidity and mortality associated with diabetes, prevention of complications is a key issue and, therefore, it is essential to understand the basic mechanisms that lead to tissue damage.

Aim of the work

The aim of our study was to detect the association between patient comorbidities, chronic complications, and different diabetic foot types for the early detection and management of these conditions.

Patients

We carried out a cross-sectional study of 80 consecutive outpatient Egyptian patients with diabetic foot disease in the National Institute of Diabetes and Endocrinology.

Results

Sixty-three percent were purely neuropathic, followed by 19% that were neuroischemic, whereas 18% were of the ischemic type. Hypertension is the most common comorbid condition and coronary artery disease is highly prevalent in the ischemic and neuroischemic types. The coexistence of hypercholesterolemia, smoking, diabetes, and male sex appears to significantly increase the incidence of ischemic diabetic foot. Nephropathy and retinopathy are significantly associated with neuropathic foot ulcers. Hypertriglyceridemia correlates positively to ischemic and neuroischemic ulcers whereas low HDL and proteinuria correlate positively to both neuropathic and neuroischemic ulcers.

Conclusion

Special attention should be paid toward the identification of patients who are at risk of foot ulceration to help prevent foot problems. Comorbid conditions must also be identified early and managed aggressively.

A 43-year-old man presented with bony pains, repeated pathological fractures with overlying skin ulcerations, and forearm and chest wall swellings. Investigations led to the diagnosis of Erdheim–Chester disease. Treatment with low-dose prednisolone, oral everolimus, and zoledronic acid was started, with a marked improvement in his condition.